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What Do Oral Drugs Really Look Like? Dose Regimen, Pharmacokinetics, and Safety of Recently Approved Small-Molecule Oral Drugs

Dean G. Brown

2025Journal of Medicinal Chemistry7 citationsDOIOpen Access PDF

Abstract

High Resolution Image Download MS PowerPoint Slide An analysis of dose, dose frequency, human pharmacokinetics, and potential drug–drug interactions (DDI) was performed on small-molecule oral drugs approved by the FDA from 2020 to 2024 ( n = 104). Although most oral drugs are administered QD (67%), BID and TID regimens are also regularly approved (32%). First-in-class (FIC) drugs and drugs with Orphan Drug Designation (ODD) have a higher frequency of BID or TID administration compared to drugs without those designations (BID and TID = 50% for FIC drugs vs 19% for non-FIC; BID and TID = 41% for ODD vs 20% non-ODD). Most drugs are >95% plasma protein bound (58%), with a large fraction >99% bound (29%). Of these drugs, 22% have black box warnings and 42% list contraindications. An examination of DDI revealed the most frequent warning around CYP3A4 induction (60%). These findings will help medicinal chemists better understand and predict typical and nontypical profiles of oral drugs.

Topics & Concepts

DrugPharmacologyOral administrationMedicinePharmacokineticsOrphan drugOral doseFood and drug administrationCYP3A4Adverse effectDrug approvalOff-label useApproved drugMEDLINEDrug labelingOral routeIntensive care medicineClinical trialMaximum tolerated dosePharmacogenetics and Drug MetabolismStatistical Methods in Clinical TrialsPharmaceutical studies and practices
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